The mechanisms by which catecholamines stimulate glucose output in liver are being investigated utilizing the isolated rat liver parenchymal cell preparation. The effects of these agents on glycogenolysis, gluconeogenesis and glycogen synthesis in this preparation are mediated mainly by gamma-adrenergic receptors. Gamma-adrenergic activation of glucose release does not involve an inrease in cAMP or activation of cAMP-dependent protein kinase, but may involve a rise in cytosolic calcium. It is proposed to study further the role of calcium ions in gamma-adrenergic effects on glycogen phosphorylase and glycogen synthase. More work will be done to identify the glycogen metabolizing enzyme(s) primarily affected by gamma-adrenergic activation. The effects of calcium depletion and repletion on hepatocyte resonses to catecholamines will be examined. The effects of calcium on the enzymes of glycogen metabolism, especially phosphorylase kinase and cAMP-independent synthase kinase, will also be studied. The effects of gamma-adrenergic agonists on calcium movements across the plasma membrane will be explored with respect to the mechanisms involved. The nature and cellular location of gamma-adrenergic receptors will be studied.